Bench-to-Bench Bottlenecks in Translation

Higgins, Matthew J.; Thursby, Jerry G.; Thursby, Marie C.

doi:10.1126/scitranslmed.3009000

Cited by 7 publications

(1 citation statement)

References 9 publications

(6 reference statements)

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“…Meanwhile, the existing regulatory regime induces them to spend billions on extremely complex, large-molecule therapies whose full interaction with the human body is imperfectly understood, and where the rate of failure in clinical trials is correspondingly high. See Higgins et al (2014) and Roin (2014) for an explication of this idea and potential policy solutions. , 1998-2010.…”

Section: Resultsmentioning

confidence: 99%

Generic Competition and the Incentives for Early-Stage Pharmaceutical Innovation

Branstetter¹,

Chatterjee

Higgins

2014

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Over the last decade, generic penetration in the U.S. pharmaceutical market has increased substantially, providing significant gains in consumer surplus. What impact has this rise in generic penetration had on the rate and direction of early stage pharmaceutical innovation? We explore this question using novel data sources and an empirical framework that models the flow of early-stage pharmaceutical innovations as a function of generic penetration, scientific opportunity, firm innovative capability, and additional controls. While the aggregate level of early-stage drug development activity has increased, our estimates suggest a sizable, robust, negative relationship between generic penetration and earlystage pharmaceutical research activity within therapeutic markets. A 10% increase in generic penetration is associated with a 7.9% decline in all early-stage innovations in the same therapeutic market. When we restrict our sample to first-in-class pharmaceutical innovations, we find that a 10% increase in generic penetration is associated with a 4.6% decline in early-stage innovations in the same market. Our estimated effects appear to vary across therapeutic classes in sensible ways, reflecting the differing degrees of substitution between generics and branded drugs in treating different diseases. Finally, we are able to document that with increasing generic penetration, firms in our sample are shifting their R&D activity to more biologic-based (large-molecule) products rather than chemical-based (smallmolecule) products. We conclude by discussing the potential implications of our results for long-run welfare, policy, and innovation. IntroductionIn his provocative paper, "The Health of Nations," Yale University economist William Nordhaus (1999) argues that the advances in human welfare generated by better medical science over the past half century have been equal in value to the consumption increases from all other sources put together. Victor Fuchs (1982) has suggested that most of the real improvement in human health generated over this period stems from modern medicine's expanding arsenal of pharmaceutical products. While documenting these claims in a way that meets modern evidentiary standards is challenging, the work of scholars such as Frank Lichtenberg (2001, 2004, 2007) has provided evidence suggesting that the gains from pharmaceutical innovation have been very large. In the long run, global investments in pharmaceutical research have proven to be very good ones.These benefits have come with significant costs; pharmaceutical innovation is risky and expensive. These costs are passed on to consumers in the form of higher prices for branded pharmaceuticals. In recent years, prescription drug spending in the U.S. has exceeded $300 billion, an increase of $135 billion since 2001. Consumption of prescription drugs now accounts for approximately 12 percent of total health care spending (GAO, 2012). However, over this time period, generic products have accounted for an increasing share of prescription...

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Section: Resultsmentioning

confidence: 99%

Generic Competition and the Incentives for Early-Stage Pharmaceutical Innovation

Branstetter¹,

Chatterjee

Higgins

2014

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Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy

Cheng

Zhang

Guo

et al. 2016

Free Radical Biology and Medicine

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The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3β phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. All these adverse effects were significantly attenuated by FF treatment. FF also significantly increased fibroblast growth factor 21 (FGF21) expression and enhanced Nrf2 function in diabetic and non-diabetic kidneys. Moreover, FF-induced amelioration of diabetic renal damage, including the stimulation of PI3K/Akt/GSK-3β/Fyn pathway and the enhancement of Nrf2 function were abolished in FGF21-null mice, confirming the critical role of FGF21 in FF-induced renal protection. These results suggest for the first time that FF prevents the development of DN via up-regulating FGF21 and stimulating PI3K/Akt/GSK-3β/Fyn-mediated activation of the Nrf2 pathway.

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The revolution re-visited: Clinical and genetics research paradigms and the productivity paradox in drug discovery

Gittelman

2016

Research Policy

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Bench-to-Bench Bottlenecks in Translation

Abstract: Transfers of biopharmaceutical inventions between firms resets and falsely shortens calculated translation times.

Cited by 7 publications

References 9 publications

Generic Competition and the Incentives for Early-Stage Pharmaceutical Innovation

Generic Competition and the Incentives for Early-Stage Pharmaceutical Innovation

Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy

The revolution re-visited: Clinical and genetics research paradigms and the productivity paradox in drug discovery

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